Cystic Fibrosis Transmembrane Conductance Regulator Facilitates ATP Release by Stimulating a Separate ATP Release Channel for Autocrine Control of Cell Volume Regulation

Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 04/2001; 276(9):6621-30. DOI: 10.1074/jbc.M005893200
Source: PubMed


These studies provide evidence that cystic fibrosis transmembrane conductance regulator (CFTR) potentiates and accelerates regulatory volume decrease (RVD) following hypotonic challenge by an autocrine mechanism involving ATP release and signaling. In wild-type CFTR-expressing cells, CFTR augments constitutive ATP release and enhances ATP release stimulated by hypotonic challenge. CFTR itself does not appear to conduct ATP. Instead, ATP is released by a separate channel, whose activity is potentiated by CFTR. Blockade of ATP release by ion channel blocking drugs, gadolinium chloride (Gd(3+)) and 4,4'-diisothiocyanatostilbene-2,2'disulfonic acid (DIDS), attenuated the effects of CFTR on acceleration and potentiation of RVD. These results support a key role for extracellular ATP and autocrine and paracrine purinergic signaling in the regulation of membrane ion permeability and suggest that CFTR potentiates ATP release by stimulating a separate ATP channel to strengthen autocrine control of cell volume regulation.

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Available from: Tamas Jilling, Jan 08, 2016
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    • "ATP is also released from non-neuronal cells through vesicular transport [6]. Additional mechanisms for ATP release has been reported including release through stretch-activated channels, voltage-dependent and multi-channel anion transporter or permeases [7], cystic fibrosis transmembrane conductance regulator (CFTR) [8], and P2X7 receptor associated connexin and pannexin hemichannels [9]. ATP release from mouse neutrophil occurs through connexin-43 hemi channels [10]. "
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    Full-text · Article · May 2013 · Journal of Biomedical Science
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    • "Many studies have reported the involvement of ABC proteins in ATP release [21]–[23]: CFTR-regulated ATP release has been observed in a variety of native cell types, including erythrocytes and epithelial cells [24], [25], whilst transfection of carcinoma cells with CFTR or reconstitution of CFTR into lipid bilayers is associated with the appearance cAMP-dependent ATP release [26]–[28]. The mechanism by which CFTR facilitates the ATP release from muscle remains controversial: some authors have proposed that ATP leaves the cell through CFTR itself, whilst others propose that CFTR regulates the activity of a separate ATP channel protein [23], [29], [30]. "
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    Full-text · Article · Nov 2012 · PLoS ONE
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    • "Several ABC proteins are potential candidates for mediating ATP release including the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR was initially thought to mediate ATP release from several cell types including erythrocytes (Sprague et al., 1998); however, later work indicated that the CFTR regulates rather than mediates the release of ATP (Sugita et al., 1998; Watt et al., 1998; Braunstein et al., 2001). Controlled vesicular exocytosis is implicated in ATP release from many cell types including epithelial and endothelial cells (Bodin and Burnstock, 2001; Knight et al., 2002). "
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